Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme.

BACKGROUND: Pivotal Phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. METHODS: XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). RESULTS: Of 1002 patients analysed, 380 were biologic-experienced. At Week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130/274) eliminated their use by Week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. CONCLUSION: In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

Achieving clinical outcomes with benralizumab in severe eosinophilic asthma patients in a real-world setting: orbe II study.

BACKGROUND: The ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain. METHODS: ORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables. RESULTS: A total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1-Q3) follow-up duration was 19.5 (14.2-24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes. CONCLUSIONS: These data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP. TRIAL REGISTRATION: NCT04648839.

Clinical burden related to oral corticosteroid treatment of severe asthma in Spain: LEVANTE study.

BACKGROUND: Severe asthma treatment with oral corticosteroids (OCS) added to inhaled corticosteroids and a long-acting ß2-agonist (ICS-LABA) may result in more treatment burden and increased adverse effects. OBJECTIVE AND METHODS: This ambispective multicenter observational study aimed at describing the clinical burden in patients with severe asthma on stable high-dose ICS-LABA who received OCS during ≥6 months (maintenance group) or ≥2 cycles in the previous 12 months (bursts group). Data collection comprised a retrospective 12-month baseline period and 2 follow-up visits at 3 and 6 months. RESULTS: Eighty-nine patients were evaluable (30 on maintenance, 59 on bursts). At baseline, mean (SD) daily prednisone equivalent exposure in the total population was 24.6 (14.7) mg: 13.8 (9.4) mg on maintenance and 29.9 (14.3) mg on bursts. During the 6-month follow-up period, mean (SD) daily dose in the total cohort was 22.5 (18.8) mg: 17.2 (18.6) mg on maintenance and 28.4 (20.6) mg on bursts. The overall annual severe exacerbations rate during the 12-month baseline period was 2.05 per patient-year and 1.5 per patient-year over the 6-month follow-up, and frequency of hospitalizations and emergency department visits were similar on both maintenance and bursts use. CONCLUSIONS: Results show a suboptimal control of severe asthma despite such high doses of OCS and persistence of disease burden regardless of the prescribing pattern in maintenance or bursts. There is therapeutic inertia to continue using OCS despite the increased risk of adverse effects and the availability of biologics.

Heterogeneity within and between physician-diagnosed asthma and/or COPD: NOVELTY cohort.

BACKGROUND: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort. METHODS: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, and stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis. RESULTS: Of 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having a ratio of post-bronchodilator forced expiratory volume in 1 s to forced vital capacity below the lower limit of normal. Symptoms and exacerbations increased with greater physician-assessed severity and were higher in asthma+COPD. However, 24.3% with mild asthma and 20.4% with mild COPD had experienced ≥1 exacerbation in the past 12 months. Medication records suggested both under-treatment and over-treatment relative to severity. Blood eosinophil counts varied little across diagnosis and severity groups, but blood neutrophil counts increased with severity across all diagnoses. CONCLUSION: This analysis demonstrates marked heterogeneity within, and overlap between, physician-assigned diagnosis and severity groups in patients with asthma and/or COPD. Current diagnostic and severity classifications in clinical practice poorly differentiate between clinical phenotypes that may have specific risks and treatment implications.

Real-world study in severe eosinophilic asthma patients refractory to anti-IL5 biological agents treated with benralizumab in Spain (ORBE study).

BACKGROUND: Benralizumab, a monoclonal antibody targeting the human interleukin-5 (IL-5) receptor (IL-5R), was used before marketing authorisation in Spain in a real world setting as part of an early-access programme (EAP) to treat patients with severe eosinophilic asthma with prior insufficient response or intolerance to anti-IL5 treatment (mepolizumab or reslizumab). The objective of this study is to describe the patient profile candidate for treatment and to assess benralizumab effectiveness. METHODS: This is an observational, retrospective, multicentre study in severe eosinophilic asthma patients refractory to other biological agents targeting the IL-5 pathway. Baseline characteristics included closest data, from the previous 12 months, to benralizumab treatment onset (index date). Patients were followed until the last treatment dosage while EAP was active (March to December 2018). Effectiveness was evaluated versus baseline, in patients who received at least three doses, with asthma control test (ACT), Mini Asthma Quality of Life Questionnaire (MiniAQLQ), annual severe exacerbation rate, oral corticosteroids treatment (OCS) and asthma-related healthcare resources utilization. RESULTS: Twenty-seven patients treated with benralizumab were included in the analysis. Effectiveness was assessed in 19 patients. Both questionnaires showed clinically meaningful differences, i.e. ACT score ≥ 3 and MiniAQLQ score ≥ 0.5, compared with baseline [mean (SD), 3.3 (6.8) and 1.2 (1.9), respectively]. Patients treated with OCS decreased during follow-up from 88.9% (n = 24/27) at baseline to 78.9% (n = 15/19) and 31.6% (n = 6/19) had an OCS dose reduction ≥ 50%. The difference in annual severe exacerbation rate during follow-up showed a significant reduction vs. baseline (2.12 per patient-year, 95% CI 0.99-3.24, p = 0.002). The differences in annual rate of non-scheduled primary care and specialist visits during follow-up indicated a significant decrease [2.28 per patient-year (95% CI 1.55-3.01; p < 0.001) and 1.47 per patient-year (95% CI 0.65-2.30; p = 0.004), respectively], as well as the difference in annual rate of number of emergency department visits [1.18 per patient-year (95% CI 0.51-1.85; p = 0.007)]. CONCLUSIONS: These results suggest that severe eosinophilic asthma patients receiving benralizumab, presented clinically meaningful improvement in asthma control and asthma-related QoL as well as OCS dose reduction. Results also aim to significant reductions in annual severe exacerbation rates, non-scheduled primary care and specialist visits, and emergency department visits rates.

Gastrointestinal events in at-risk patients starting non-steroidal anti-inflammatory drugs (NSAIDs) for rheumatic diseases: the EVIDENCE study of European routine practice.

OBJECTIVES: Data concerning rates of gastrointestinal (GI) events in non-steroidal anti-inflammatory drug (NSAID) users derive mainly from clinical trials. The EVIDENCE study quantified the incidence of symptomatic uncomplicated and/or complicated GI events in at-risk European patients treated with NSAIDs in real-life practice. METHODS: This non-interventional study assessed 4144 adults with at least one GI risk factor who recently initiated NSAID therapy for osteoarthritis (85%), rheumatoid arthritis (11%), ankylosing spondylitis (3%) or a combination (1%). Patient characteristics and medical history were collected from medical records. GI events (upper and lower) were recorded at in-clinic visits during 6 months' follow-up. RESULTS: Mean time on index NSAID at enrolment was 33 days. The incidence (per 100 person-years) was 18.5 per 100 person-years for uncomplicated GI events and 0.7 per 100 person-years for complicated GI events. Upper GI events were far more common (12%) than lower GI events (1%) during study follow-up (median 182 days (range 61-320)). Other reported rates for cardiovascular, anaemia or non-GI events were much less frequent. A minority (28%) of patients had ongoing proton pump inhibitor use at enrolment, with strong variation by practice and country. CONCLUSIONS: EVIDENCE is the largest prospective study of the real-life management of European patients treated with NSAIDs for rheumatic diseases and at increased GI risk. It shows that GI events from the upper GI tract are far more common than those from the lower GI tract. It also shows adherence to guidelines for gastroprotection is generally low. CLINICALTRIALSGOV IDENTIFIER: NCT01176682.

Impact of COPD Exacerbations and Burden of Disease in Spain: AVOIDEX Study.

Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity and mortality, with a considerable consumption of healthcare resources (HRU). This study aims to obtain real world evidence regarding the consequences of COPD exacerbations and to provide updated data on the burden of this disease and its treatment. Patients and Methods: A retrospective study in seven Spanish regions was conducted among COPD patients diagnosed between 1/01/2010 and 31/12/2017. The index date was the diagnosis of COPD and patients were followed until lost to follow-up, death or end of the study, whichever occurred first. Patients were classified by patient pattern (incident or prevalent), type and severity of exacerbations, and treatments prescribed. Demographic and clinical characteristics were evaluated, together with the incidence of exacerbations, comorbidities, and the use of HRU, during the baseline (12 months before the index date) and the follow-up periods by incident/prevalent and treatment prescribed. Mortality rate was also measured. Results: The study included 34,557 patients with a mean age of 70 years (standard deviation: 12). The most frequent comorbidities were diabetes, osteoporosis, and anxiety. Most patients received inhaled corticosteroids (ICS) with long-acting beta agonists (LABA), or long-acting muscarinic agonists (LAMA), followed by LABA with LAMA. Incident patients (N=8229; 23.8%) had fewer exacerbations than prevalent patients (N=26328; 76.2%), 0.3 vs 1.2 exacerbations per 100 patient-years. All treatment patterns present a substantial disease burden, which seems to increase with the evolution of the disease (ie moving from initial treatments to combination therapies). The overall mortality rate was 40.2 deaths/1000 patient-years. General practitioner visits and tests were the HRU most frequently required. The frequency and severity of exacerbations positively correlated with the use of HRU. Conclusion: Despite receiving treatment, patients with COPD suffer a considerable burden mainly due to exacerbations and comorbidities, which require a substantial use of HRU.

Effect of Stepping Up to High-Dose Inhaled Corticosteroids in Patients With Asthma: UK Database Study.

BACKGROUND: It is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICSs). OBJECTIVE: To determine the effectiveness of stepping up to high-dose ICSs. METHODS: A historic cohort study of patients with asthma (≥13 years old), identified from 2 large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICSs were compared with those who stepped up from medium- to high-dose ICSs, whereas patients who stepped up from low- to medium-dose ICSs were compared with those who stepped up from low- to high-dose ICSs. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and the number of exacerbations and antibiotics courses was analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding. RESULTS: The mean follow-up time to first exacerbation was 2.7 ± 2.7 years for those who remained on stable medium-dose ICSs and 2.0 ± 2.2 years for those who stepped up from medium- to high-dose ICSs. A similar pattern was noted for those who stepped up from low- to medium-dose ICSs (2.6 ± 2.5 years) and from low- to high-dose ICSs (2.3 ± 2.5 years). Patients who stepped up from medium- to high-dose ICSs (n = 6879) had a higher risk of exacerbations during follow-up compared with those who remained on medium-dose ICSs (n = 51,737; hazard ratio, 1.17; 95% CI, 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n = 3232) compared with low- to medium-dose (n = 12,659) ICSs (hazard ratio, 1.10; 95% CI, 1.04-1.17). A step-up to high-dose ICSs was also associated with a higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts. CONCLUSIONS: We found no evidence that a step-up to high-dose ICSs is effective in preventing future asthma exacerbations.

[Current management of nonvariceal upper gastrointestinal bleeding in Spain]. / Situación actual del manejo de la hemorragia digestiva alta no varicosa en España.

BACKGROUND: Mortality related to nonvariceal upper gastrointestinal bleeding (NVUGIB) has not changed. More information is needed to improve the management of this entity. The aims of this study were: a) to determine the characteristics of bleeding episodes, b) to describe the clinical approaches routinely used in NVUGIB, and c) to identify adverse outcomes related to endoscopic or medical treatments in Spain. METHODS: The European survey of nonvariceal upper GI bleeding (ENERGiB) was an observational, retrospective cohort study on NVUGIB with endoscopic evaluation carried out across Europe. The present study focused on Spanish patients in the ENERGiB study. The patients were managed according to routine care. The mean and standard deviation were calculated for quantitative variables and absolute and relative frequencies were calculated for categorical variables. RESULTS: Patients (n=403) were mostly men (71%), with a mean age of 65 years, and co-morbidities (62.5%). Most of the patients were managed by gastroenterologists (57.1%) or internal medicine teams (25.1%). A proton pump inhibitor was used empirically in 80% before endoscopy. Bleeding persistence occurred in 6.4% and recurrence in 6.7%. The mortality rate at 30 days was 3.5%. CONCLUSIONS: This study contributes to the characterization of Spanish patients and NVUGIB episodes in a real clinical setting and identifies the routine management of this entity, which is in line with the standards proposed by recent clinical practice guidelines. A notable finding was that age and the number of comorbidities in NVUGIB patients were increasing. These factors could explain the persistent mortality rate, despite the evident advances in the management of this entity.

Short-Acting Beta-2-Agonist Exposure and Severe Asthma Exacerbations: SABINA Findings From Europe and North America.

BACKGROUND: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists. OBJECTIVE: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe. METHODS: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations. RESULTS: Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5-treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2-treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy-treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5-treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications. CONCLUSIONS: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

Factors associated with a higher prevalence of work disability among asthmatic patients.

OBJECTIVE: To study asthma-related absenteeism in the asthmatic population in Spain and to identify some risk factors for absenteeism. METHODS: A cross-sectional study was performed on patients who had been diagnosed with asthma in the primary care setting at least 1 year before the start of this study. A questionnaire was designed that included socio-demographic and clinical variables. The time absent from work in the previous year was self-reported by the patients. RESULTS: More than 25% of the asthmatic population in Spain took sick leave during the previous year. Visits to a general practitioner or to the emergency department are the factors associated with the greatest risk of absenteeism. CONCLUSIONS: Absenteeism is common within the asthmatic population in Spain. The authors of this study believe that some of the determining factors could be modified by the health-care system.

[Use of health resources and loss of productivity in gastroesophageal reflux disease: results of a cross-sectional study in a primary care setting in Spain]. / Consumo de recursos sanitarios y pérdida de productividad en la enfermedad por reflujo gastroesofágico: resultados de un estudio transversal en el ámbito de la atención primaria en España.

OBJECTIVE: To evaluate healthcare resource use and productivity in patients with gastro-esophageal reflux disease (GERD) and the influence of disease severity on these two factors. DESIGN: Sub-analysis of the Spanish population of a multinational study with a 4-month retrospective period for the identification and selection of patients, and a clinical visit to obtain clinical information and data on use of healthcare resources, carried out between October 2007 and January 2008. POPULATION: A total of 477 patients attending a Primary Care centre, with a medical consultation for GERD. MAIN VARIABLES: Use of healthcare resources, changes in productivity based on the Work Productivity and Activity Impairment Questionnaire for GERD patients (WPAI-GERD). RESULTS: Despite having received pharmacological treatment at the baseline visit, after a median of 5.1 months follow-up (range 2.1-8.1), up to 15.9% (95% CI; 12.8-19.5) patients still showed clinically relevant GERD symptoms. Direct medical costs per year associated with diagnostic tests and medical consultations in patients with or without clinically relevant GERD symptoms were 666 € (SD: 2,097 €) and 370 € (SD: 2,060 €), respectively. The mean annual cost of reduced productivity (17%) was 5,316 € (SD: 8,615 €). This cost was 4 times higher for patients with clinically relevant GERD symptoms than for patients with no relevant symptoms (15,188 € [SD: 11,206 €] vs 3,926 € [SD: 7,232 €]). CONCLUSION: Patients with GERD use significant healthcare resources, attributable to associated medical costs and marked reduction in productivity, even though they receive pharmacological treatment.

[Study of the clinical profile and management of patients with gastroesophageal reflux disease in primary care in Spain]. / Estudio de síntomas relevantes y atención clínica en la enfermedad por reflujo gastroesofágico en atención primaria en España.

OBJECTIVE: To assess the clinical profile and management of patients with gastroesophageal reflux disease (GERD) in primary care. METHODS: A multinational, multicenter study was performed comprising a 4-month retrospective phase for the screening, selection and assessment of patients who had consulted for any GERD-related cause (index visit), and a cross-sectional phase in which clinical data were recorded and the following questionnaires were administered: the Reflux Disease Questionnaire and the Gastroesophageal Reflux Disease Impact Scale (GIS). RESULTS: Among the 24 participating Spanish centers, 2.7% of the patients (95% CI: 2.6-2.9) had consulted at least once because of GERD. Approximately 50% of the patients showed frequent (2 or more days a week) or moderate to severe symptoms of heartburn, acid regurgitation or chest pain. Although the patients received effective pharmacological treatment at the index visit, clinically relevant GERD symptoms persisted in 16% after a median follow-up of 5 months. These symptoms were associated with a strong disease impact as evaluated with the GIS. CONCLUSION: GERD represents a substantial burden for primary care physicians. Although effective drugs are used for the treatment of this condition, clinically relevant symptoms persist in a substantial proportion of patients.

Observational studies assessing the pharmacological treatment of obstructive lung disease: strengths, challenges and considerations for study design.

Randomised controlled trials (RCTs) are the gold standard for evaluating treatment efficacy in patients with obstructive lung disease. However, due to strict inclusion criteria and the conditions required for ascertaining statistical significance, the patients included typically represent as little as 5% of the general obstructive lung disease population. Thus, studies in broader patient populations are becoming increasingly important. These can be randomised effectiveness trials or observational studies providing data on real-world treatment effectiveness and safety data that complement efficacy RCTs. In this review we describe the features associated with the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in the real-world clinical practice setting. We also discuss how RCTs and observational studies have reported opposing outcomes with several treatments and inhaler devices due to differences in study design and the variations in patients recruited by different study types. Whilst observational studies are not without weaknesses, we outline recently developed tools for defining markers of quality of observational studies. We also examine how observational studies are capable of providing valuable insights into disease mechanisms and management and how they are a vital component of research into obstructive lung disease. As we move into an era of personalised medicine, recent observational studies, such as the NOVEL observational longiTudinal studY (NOVELTY), have the capacity to provide a greater understanding of the value of a personalised healthcare approach in patients in clinical practice by focussing on standardised outcome measures of patient-reported outcomes, physician assessments, airway physiology, and blood and airway biomarkers across both primary and specialist care.

Real-life retrospective observational study to determine the prevalence and economic burden of severe asthma in Spain.

Objective: We determined the percentage of patients with severe asthma and exacerbations and evaluated the costs of the disease based on blood eosinophil counts.Methods: A retrospective observational study based on the review of medical records in Spain was carried out. Patients ≥18 years of age requiring care during the years 2014-2015; diagnosed with asthma with at least 2 years of continuous records (at least one year prior to the index date defined as the first asthma medication prescription and at least one year after the index date) were included. Study groups: eosinophil counts <300 cells/µl and ≥300 cells/µl. Main variables: comorbidity, clinical parameters, exacerbations and annual asthma total costs.Results: A total of 268 severe asthmatic patients in Spain were included, representing 6.3% of the asthma population, with 58.6% having eosinophil count ≥300 cells/µl and 41.4% eosinophil count <300 cells/µl. The mean age was 56.1 years (63.4% women). Patients with eosinophilic inflammation (≥300 cells/µl) had lower FEV1 values (54.3% vs. 60.7%; p < .001), poorer treatment adherence (65.6% vs. 77.3%; p < .001), and a greater mean number of exacerbations (3.3 vs. 1.9; p < .001). Exacerbations were correlated to FEV1 (ß=‒.606), eosinophils (ß = .255), immunoglobulin E (ß = .152), and age (ß = .128), p < .001. The mean total asthma annual cost (ANCOVA) was 6222 vs. 4152 euros, respectively (p = .016). Health costs were associated with age (ß = .323), FEV1 (ß = .239), eosinophils (ß = .177) and exacerbations (ß = .158), p < .01.Limitations: Those inherent to retrospective studies; the possible inaccuracy of diagnostic coding referring to severe asthma and other comorbidities and the external validity of the results.Conclusions: Health costs of patients with severe asthma were high. Total annual asthma costs and resource use were greater in patients with ≥300 cells/µl. Age, eosinophilia, exacerbations and FEV1 were associated with greater resource utilization and costs for the health system.

SABINA: An Overview of Short-Acting ß2-Agonist Use in Asthma in European Countries.

INTRODUCTION: Globally, individuals with asthma tend to overrely on short-acting ß2-agonists (SABAs) and underuse inhaled corticosteroids, thereby undertreating the underlying inflammation. Such relief-seeking behavior has been reinforced by long-standing treatment guidelines, which until recently recommended SABA-only use for immediate symptom relief. We aimed to describe the current burden of SABA use among European individuals with asthma within the SABA use IN Asthma (SABINA) program. METHODS: Prescription and/or dispensing data during 2006-2017 from electronic medical records and/or national patient registries in the United Kingdom (UK), Germany, Italy, Spain, and Sweden were analyzed. Individuals aged at least 12 years old with a current asthma diagnosis and no other chronic respiratory conditions were included. Asthma treatment step and severity were based on treatment guidelines in use in each individual country. The proportion of individuals prescribed SABA was measured during a 12-month period. SABA overuse was defined as at least three SABA canisters per year. RESULTS: More than one million individuals with asthma were included across five European countries. Overall, the majority of individuals were over 45 years of age, except in Sweden (mean age 27.6 years) where individuals aged over 45 years were excluded to avoid a potential chronic obstructive pulmonary disease co-diagnosis. The study population was predominantly female (55-64%), except in the UK (46%). The prevalence of SABA overuse was 9% in Italy, 16% in Germany, 29% in Spain, 30% in Sweden, and 38% in the UK. In the UK, SABA overuse was greater in individuals with moderate-to-severe asthma versus individuals with mild asthma (58% versus 27%, respectively), while SABA overuse was similar in individuals with both mild (9-32%) and moderate-to-severe (8-31%) asthma in the other European countries. CONCLUSIONS: The findings of this study from the SABINA program show that SABA overuse (at least three canisters per year) is common across Europe, despite the different healthcare and reimbursement policies of each country.

Impact of gastroesophageal reflux disease on work absenteeism, presenteeism and productivity in daily life: a European observational study.

BACKGROUND: The RANGE (Retrospective ANalysis of GastroEsophageal reflux disease [GERD]) study assessed differences among patients consulting a primary care physician due to GERD-related reasons in terms of: symptoms, diagnosis and management, response to treatment, and effects on productivity, costs and health-related quality of life. This subanalysis of RANGE determined the impact of GERD on productivity in work and daily life. METHODS: RANGE was conducted at 134 primary care sites across six European countries (Germany, Greece, Norway, Spain, Sweden and the UK). All subjects (aged >or=18 years) who consulted with their primary care physician over a 4-month identification period were screened retrospectively, and those consulting at least once for GERD-related reasons were identified (index visit). From this population, a random sample was selected to enter the study and attended a follow-up appointment, during which the impact of GERD on productivity while working (absenteeism and presenteeism) and in daily life was evaluated using the self-reported Work Productivity and Activity Impairment Questionnaire for patients with GERD (WPAI-GERD). RESULTS: Overall, 373,610 subjects consulted with their primary care physician over the 4-month identification period, 12,815 for GERD-related reasons (3.4%); 2678 randomly selected patients attended the follow-up appointment. Average absenteeism due to GERD was highest in Germany (3.2 hours/week) and lowest in the UK (0.4 hours/week), with an average of up to 6.7 additional hours/week lost due to presenteeism in Norway. The average monetary impact of GERD-related work absenteeism and presenteeism were substantial in all countries (from euro55/week per employed patient in the UK to euro273/patient in Sweden). Reductions in productivity in daily life of up to 26% were observed across the European countries. CONCLUSION: GERD places a significant burden on primary care patients, in terms of work absenteeism and presenteeism and in daily life. The resulting costs to the local economy may be substantial. Improved management of GERD could be expected to lessen the impact of GERD on productivity and reduce costs.

[Validation of the Reflux Disease Questionnaire (RDQ) and Gastrointestinal Impact Scale (GIS) in patients with gastroesophageal reflux disease in the Spanish population]. / Validación del Cuestionario sobre Alteraciones de Reflujo (RDQ) y de la Escala de Impacto de la Enfermedad por Reflujo Gastroesofágico (GIS) para población española.

OBJECTIVES: To assess the feasibility, reliability, validity and sensitivity of changes in the Reflux Disease Questionnaire (RDQ) and the Gastrointestinal Impact Scale (GIS). MATERIAL AND METHODS: An observational, prospective, multicenter study was conducted in primary care centers on two visits (baseline and 16 days later) in a sample of patients with a diagnosis of gastroesophageal reflux disease (GERD) or suspicion of GERD requiring a therapeutic intervention (sensitivity to change group, n=230) and in another sample of patients with clinically controlled GERD (reliability group, n=51). RESULTS: The RDQ questionnaire and GIS scale, both overall and for each domain, showed a Cronbach's alpha of greater than or equal to 0.70. All RDQ domains and the total score, as well as the total GIS score and impact dimension, showed a high correlation between the baseline evaluation and that performed 16 days later in stable patients. The RDQ and GIS showed very high correlations between the total scores and those of the quality of life in reflux and dyspepsia (QOLRAD) (-0.73 and 0.80, respectively), a reflux- and dyspepsia-specific quality of life scale, and a high correlation with the gastrointestinal symptoms rating scale (GSRS) (0.54 and -0.55, respectively), a general scale of gastrointestinal symptoms. Both the RDQ questionnaire and the GIS scale showed significant changes with a high effect size on improvement responses. CONCLUSIONS: The RDQ and GIS questionnaires show very good psychometric properties, making them suitable for use in primary care.

The economic burden of uncontrolled gout: how controlling gout reduces cost.

AIM: To evaluate the burden of uncontrolled gout by examining estimated costs and cost drivers. MATERIALS AND METHODS: Data from the 2012 and 2013 US National Health and Wellness Survey (NHWS; 2012 NHWS, n = 71,157 and 2013 NHWS, n = 75,000) were utilized in this study. Based on self-reported gout diagnosis and gout symptoms, respondents were categorized into three groups: controlled gout (n = 344), uncontrolled gout (n = 2,215), and non-gout controls (n = 126,360). Chi-square tests and one-way analysis of variance (ANOVAs) were used to assess group differences on work productivity loss, healthcare resource utilization, and costs. Zero-inflated negative binomial regressions were used to assess the burden of uncontrolled gout on total costs after controlling for covariates. RESULTS: Patients with uncontrolled gout had higher presenteeism, overall work impairment, activity impairment, and number of emergency department visits than those with controlled gout or controls. Overall, uncontrolled gout patients had both higher indirect and total costs compared to patients with controlled gout. After controlling for confounders, those with uncontrolled gout had higher total costs than controlled gout respondents and non-gout controls; there was no significant difference in total costs between patients with controlled gout and non-gout controls. LIMITATIONS: Results were based on cross-sectional, self-reported data, making causal inferences more uncertain. Additionally, sample size was small for controlled-gout respondents. Lastly, sampling weights were not used, thus potentially limiting generalizability. CONCLUSION: Gout can be an expensive condition, particularly if it is not properly controlled. This study provides support that controlling symptoms (e.g. flares) can reduce the economic and societal burden of gout. Therefore, more attention needs to be paid to effective management of gout symptoms.

Use of aclidinium did not increase the risk of death in a noninterventional cohort study in the Clinical Practice Research Datalink (CPRD), United Kingdom.

BACKGROUND: Aclidinium bromide is an inhaled long-acting muscarinic antagonist (LAMA). Although the initial potential increased cardiovascular and mortality risk among users of tiotropium has been ruled out by several observational studies, and clinical trials, there are still concerns related to the use of newer LAMA medications. The current study aimed to evaluate the risk of death among users of aclidinium and other LAMAs. METHODS: We conducted a cohort and nested case-control study among patients with COPD aged 40 years or older to compare the risk of all-cause mortality among users of aclidinium and other COPD medications with the risk among users of long-acting ß2 agonists (LABA), in the Clinical Practice Research Datalink (CPRD) in the United Kingdom (2012-2017). RESULTS: Mortality rates per 1,000 person-years were 32.9 for aclidinium, 43.8 for tiotropium, 38.0 for other LAMA, 47.1 for LABA/ICS, and 38.1 for LABA. The RR of death compared with current use of LABA was 0.54 (confidence interval [95% CI], 0.40-0.72) for aclidinium, 0.96 (95% CI, 0.76-1.21) for tiotropium, 0.76 (95% CI, 0.58-0.99) for other LAMA, and 1.08 (95% CI, 0.90-1.31) for LABA/ICS. Decreased risk for death observed among users of aclidinium was driven by overall current single use (RR = 0.41; 95% CI, 0.22-0.79), which corresponded to 26% of the aclidinium users (<15 cases) and not by multiple use (RR = 1.02; 95% CI, 0.71-1.48). CONCLUSION: Use of aclidinium, tiotropium, other LAMA, or LABA/ICS was not associated with an increased risk of all-cause mortality as compared with the use of LABAs.